Journal article
Comparative Effectiveness of Anti-TNF in Combination with Low Dose Methotrexate vs Anti-TNF Monotherapy in Pediatric Crohn’s Disease: a Pragmatic Randomized Trial
Gastroenterology (New York, N.Y. 1943), Vol.165(1), pp.149-161.e7
07/2023
DOI: 10.1053/j.gastro.2023.03.224
PMCID: PMC10330864
PMID: 37004887
Abstract
Tumor Necrosis Factor inhibitors (TNFi), including infliximab and adalimumab, are a mainstay of pediatric Crohn’s disease (PCD) therapy; however, non-response and loss of response is common. As combination therapy with methotrexate may improve response, we performed a multi-center, randomized, double-blind, placebo-controlled pragmatic trial to compare TNFi with oral methotrexate to TNFi monotherapy.
PCD patients initiating infliximab or adalimumab were randomized in 1:1 allocation to methotrexate or placebo and followed for 12-36 months. The primary outcome was a composite indicator of treatment failure. Secondary outcomes included anti-drug antibodies (ADA) and patient reported outcomes (PROs) of pain interference and fatigue. Adverse events (AEs) and Serious AEs (SAEs) were collected.
Of 297 participants (mean age 13.9 years, 35% female), 156 were assigned to methotrexate (110 infliximab initiators and 46 adalimumab initiators) and 141 to placebo (102 infliximab initiators and 39 adalimumab initiators). In the overall population, time to treatment failure did not differ by study arm (HR 0.69, 95% CI 0.45-1.05). Among infliximab initiators, there were no differences between combination and monotherapy (HR 0.93, 95% CI 0.55-1.56). Among adalimumab initiators, combination therapy was associated with longer time to treatment failure (HR 0.40, 95% CI 0.19-0.81). A trend towards lower ADA development in the combination therapy arm was not significant. [(infliximab OR 0.72 (0.49-1.07); adalimumab OR 0.71 (0.24-2.07)]. No differences in PROs were observed. Combination therapy resulted in more AEs but fewer SAEs.
Among adalimumab but not infliximab initiators, PCD patients treated with methotrexate combination therapy experienced a 2-fold reduction in treatment failure with a tolerable safety profile.
Details
- Title: Subtitle
- Comparative Effectiveness of Anti-TNF in Combination with Low Dose Methotrexate vs Anti-TNF Monotherapy in Pediatric Crohn’s Disease: a Pragmatic Randomized Trial
- Creators
- Michael D. Kappelman - University of North Carolina at Chapel HillDavid A. Wohl - University of North Carolina at Chapel HillHans H. Herfarth - Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NCAnn M. Firestine - University of North Carolina at Chapel HillJeremy Adler - University of MichiganRana F. Ammoury - Children's Hospital of The King's DaughtersJeanine E. Aronow - Cincinnati Children's Hospital Medical CenterDorsey M. Bass - Stanford University School of MedicineJulie A. Bass - University of Missouri–Kansas CityKeith Benkov - Division of Pediatric Gastroenterology, Icahn School of Medicine at Mt Sinai, New York City, NYCatalina Berenblum Tobi - University of North Carolina at Chapel HillMargie E. Boccieri - University of North Carolina at Chapel HillBrendan M. Boyle - Nationwide Children's HospitalWilliam B. BrinkmanJose M. Cabera - Children's Hospital of WisconsinKelly Chun - LabCorp (United States)Richard B. Colletti - University of VermontCassandra M. Dodds - Cincinnati Children's Hospital Medical CenterJill M. Dorsey - Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Nemours Children's Health, Jacksonville, FLDawn R. Ebach - University of IowaEdurne Entrena - Progenika Biopharma, a Grifols Company, Derio, Bizkaia SpainChristopher B. Forrest - Children's Hospital of PhiladelphiaJoseph A. Galanko - University of North Carolina School of MedicineJohn E. Grunow - University of OklahomaAjay S. Gulati - University of North Carolina at Chapel HillAnastasia Ivanova - University of North Carolina at Chapel HillTraci W. Jester - University of Alabama at BirminghamJess L. Kaplan - Harvard Medical SchoolSubra Kugathasan - Emory UniversityMark E. Kusek - University of Nebraska Medical CenterIan H. Leibowitz - George Washington UniversityTiffany M. Linville - Levine Children's HospitalEllen A. Lipstein - University of CincinnatiPeter A. Margolis - University of CincinnatiPhillip Minar - University of CincinnatiZarela Molle Rios - Division of Pediatric Gastroenterology, Nemours Children’s Hospital, Wilmington, DEJonathan Moses - Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, UH Rainbow Babies and Children's Hospital, Cleveland, OHKelly K. Olano - Cincinnati Children's Hospital Medical CenterLourdes Osaba - Progenika Biopharma, a Grifols Company, Derio, Bizkaia SpainPablo J. Palomo - Division of Pediatric Gastroenterology, Nemours Children's Hospital, Orlando, FLHelen Pappa - Division of Pediatric Gastroenterology, Cardinal Glennon Children's Hospital, Saint Louis University School of Medicine, Saint Louis, MOK.T. Park - Stanford University School of MedicineDinesh S. Pashankar - University of New HavenLisa Pitch - ImproveCareNow Inc., Essex Junction, VTMichelle Robinson - University of North Carolina at Chapel HillCharles M. Samson - Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Washington University School of Medicine, St. Louis, MOKelly C. Sandberg - Wright State UniversityJulia R. Schuchard - Children's Hospital of PhiladelphiaMichael SeidKimberly A. Shelly - Indiana UniversitySteven J. Steiner - Indiana UniversityJennifer A. Strople - Lurie Children's HospitalJillian S. Sullivan - University of Vermont Children’s HospitalJeanne Tung - University of OklahomaPrateek Wali - SUNY Upstate Medical UniversityMichael Zikry - LabCorp (United States)Morris Weinberger - University of North Carolina at Chapel HillShehzad A. Saeed - Wright State UniversityAthos Bousvaros - Boston Children's Hospital
- Resource Type
- Journal article
- Publication Details
- Gastroenterology (New York, N.Y. 1943), Vol.165(1), pp.149-161.e7
- DOI
- 10.1053/j.gastro.2023.03.224
- PMID
- 37004887
- PMCID
- PMC10330864
- NLM abbreviation
- Gastroenterology
- ISSN
- 0016-5085
- eISSN
- 1528-0012
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000069, name: National Institute of Arthritis and Musculoskeletal and Skin Diseases; DOI: 10.13039/100006093, name: Patient-Centered Outcomes Research Institute; DOI: 10.13039/100007028, name: Leona M and Harry B Helmsley Charitable Trust
- Language
- English
- Electronic publication date
- 03/31/2023
- Date published
- 07/2023
- Academic Unit
- Stead Family Department of Pediatrics; Gastroenterology, Hepatology, Pancreatology, and Nutrition
- Record Identifier
- 9984386254802771
Metrics
113 Record Views